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Mechanisms of Morbid Hearing Loss Associated with Tumors of the Endolymphatic Sac in Von Hippel-Lindau Disease

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Mechanisms of Morbid Hearing Loss Associated with Tumors of the Endolymphatic Sac in Von Hippel-Lindau Disease ORIGINAL CONTRIBUTION Mechanisms of Morbid Hearing Loss Associated With Tumors of the Endolymphatic Sac in von Hippel-Lindau Disease John A. Butman, MD, PhD Context Endolymphatic sac tumors (ELSTs) are associated with von Hippel-Lindau H. Jeffrey Kim, MD disease and cause irreversible sensorineural hearing loss (SNHL) and vestibulopathy. Martin Baggenstos, MD The underlying mechanisms of audiovestibular morbidity remain unclear and optimal timing of treatment is not known. Joshua M. Ammerman, MD Objective To define the mechanisms underlying audiovestibular pathophysiology James Dambrosia, PhD associated with ELSTs. Athos Patsalides, MD Design, Setting, and Patients Prospective and serial evaluation of patients with Nicholas J. Patronas, MD von Hippel-Lindau disease and ELSTs at the National Institutes of Health between May 1990 and December 2006. Edward H. Oldfield, MD Main Outcome Measures Clinical findings and audiologic data were correlated Russell R. Lonser, MD with serial magnetic resonance imaging and computed tomography imaging studies NDOLYMPHATIC SAC TUMORS to determine mechanisms underlying audiovestibular dysfunction. (ELSTs) are highly vascular, be- Results Thirty-five patients with von Hippel-Lindau disease and ELSTs in 38 ears (3 nign, but locally aggressive neo- bilateral ELSTs) were identified. Tumor invasion of the otic capsule was associated with plasms of the endolymphatic larger tumors (P=.01) and occurred in 7 ears (18%) causing SNHL (100%). No evi- Esystem that often destroy the surround- dence of otic capsule invasion was present in the remaining 31 ears (82%). SNHL de- veloped in 27 of these 31 ears (87%) either suddenly (14 ears; 52%) or gradually (13 ing temporal bone (FIGURE 1).1-3 ELSTs ears; 48%) and 4 ears had normal hearing. Intralabyrinthine hemorrhage was found occur sporadically but are a common in 11 of 14 ears with sudden SNHL (79%; PϽ.001) but occurred in none of the 17 manifestation of von Hippel-Lindau dis- ears with gradual SNHL or normal hearing. Tumor size was not related to SNHL (P=.23) ease (VHL), in which they can also oc- or vestibulopathy (P=.83). cur bilaterally.3,4 ELSTs are associated Conclusions ELST-associated SNHL and vestibulopathy may occur suddenly due to with significant audiovestibular mor- tumor-associated intralabyrinthine hemorrhage, or insidiously, consistent with endo- bidity, including sudden irreversible lymphatic hydrops. Both of these pathophysiologic mechanisms occur with small tu- hearing loss.3-5 Despite the effects of mors that are not associated with otic capsule invasion. ELSTs and their association with VHL, JAMA. 2007;298(1):41-48 www.jama.com the underlying pathophysiologic mechanisms of audiovestibular dys- cols in patients with VHL including se- Information from these evaluations now function associated with ELSTs, the rial high-resolution magnetic resonance provides insight into the mechanisms high incidence of unexplained audio- imaging (MRI) and computed tomo- of symptom formation, early imaging vestibular dysfunction in patients with graphic (CT) imaging with audiologic features, and the natural history of VHL, and the optimal timing of treat- evaluations have been developed and ELSTs. To determine the mechanisms ment for ELSTs have not been de- used at the National Institutes of Health. underlying hearing loss and other ves- fined. Since clinicians have determined the Author Affiliations: Diagnostic Radiology Depart- Biostatistics Branch (Dr Dambrosia), National Insti- presence of ELSTs in the VHL syn- ment, The Clinical Center of the National Institutes tute of Neurological Disorders and Stroke, National of Health (Drs Butman, Patsalides, and Patronas); Institutes of Health, Bethesda, Maryland. drome, prospective screening proto- Neuro-Otology Branch, National Institute on Deaf- Corresponding Author: John A. Butman, MD, PhD, ness and Other Communication Disorders, National Diagnostic Radiology Department, The Clinical Cen- See also Patient Page. Institutes of Health (Dr Kim); Surgical Neurology Branch ter of the National Institutes of Health, Bldg 10, Room (Drs Baggenstos, Ammerman, Oldfield, and Lonser), 1C365, Bethesda, MD 20892 ([email protected]). ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, July 4, 2007—Vol 298, No. 1 41 Downloaded from www.jama.com on July 3, 2007 HEARING LOSS ASSOCIATED WITH TUMORS IN VON HIPPEL-LINDAU DISEASE tibulopathy in patients with ELSTs, we CT Imaging steady state acquisition, and 3- to 5-mm analyzed the serial imaging and clini- To determine the presence of otic cap- fluid-attenuated inversion recovery. Im- cal findings in consecutive patients with sule invasion and extent of bony ero- age resolution was less than 1 mm in VHL with ELSTs. sion by ELSTs, temporal bone CT plane in all cases. imaging (axial and coronal; 0.625- to Because the contents of the vestibu- 1.5-mm slice thickness; bone algorithm lar aqueduct may normally enhance on METHODS reconstruction kernel) was performed. high-resolution postcontrast T1- Patients For analysis purposes, ELSTs were di- weighted spoiled gradient recall se- Clinic charts, audiograms, MRI, and CT vided into 2 groups based on CT imaging quences, small in situ ELSTs were iden- images were analyzed for patients with evidence of otic capsule invasion by tu- tified by asymmetrical enhancement of VHL whose cases were monitored at the mor or lack thereof. the endolymphatic duct on MRI to- National Institutes of Health between gether with bony erosion of the ves- May 25, 1990, and December 18, 2006. Magnetic Resonance Imaging tibular aqueduct on CT imaging. The All patients were studied under Na- Inner ear MRI was used to identify the presence of intralabyrinthine hemor- tional Institute of Neurological Disor- extent of soft tissue mass in the tem- rhage was defined on MRI as abnor- ders and Stroke internal review board– poral bone and to evaluate signal within mal isolated intralabyrinthine increased approved protocols (NIH 79-N-0089 the sensory labyrinth. Because the stud- signal on precontrast T1-weighted im- and NIH 00-N-0140) after providing in- ies spanned several years, there was ages. Intralabyrinthine lipoma, which formed consent. Patients were prospec- some variation in technique commen- could also appear as a precontrast T1- tively monitored for the development surate with technical improvements in weighted hyperintensity, was ex- of audiovestibular symptoms and in- methodology. Before 1999, MRI in- cluded on fat-saturated MRI. To quan- cluded if diagnostic imaging showed cluded spin echo T1-weighted precon- tify and compare tumor size, the largest evidence of ELST. trast and postcontrast and fast spin echo tumor diameter was determined from T2-weighted sequences using slice a single axial slice using MRI and re- Imaging Studies thickness of 3 mm or less. After 1999, corded. Neuroradiologists blinded to the pres- examinations used 1.6-mm overlap- ence and degree of audiovestibular find- ping spoiled gradient recall T1- Clinical Evaluation ings reviewed all imaging studies and weighted precontrast and postcon- Patients underwent complete neurologic recorded the results. trast, T2-weighted fast induction of andaudiologicexaminations(see“Audio- Figure 1. Anatomical Relationships of the Endolymphatic Sac LRLeft Inner Ear, Superoposterior View Left Inner Ear, Axial Cross Section Cochlea Utricle Saccule Carotid AREA OF Otic capsule Tympanic artery DETAIL External auditory cavity canal Cochlea CNVII Membranous Vestibule labyrinth Semicircular CNVIII canals CNVIII MASTOID PETROUS AIR CELLS CNVII TEMPORAL BONE Vestibule Otic capsule (DURA REMOVED) Vestibular aqueduct Posterior semicircular canal Endolymphatic duct Endolymphatic duct DUR A (in vestibular aqueduct) LEVEL OF AXIAL CROSS SECTION Endolymphatic Sigmoid sac Endolymphatic sinus Sigmoid sinus sac The endolymphatic sac is located on the posteromedial surface of the petrous temporal bone, covered by dura. The endolymphatic duct lies within the vestibular aqueduct and connects the endolymphatic sac to the remainder of the membranous labyrinth. The bony otic capsule encases the membranous labyrinth. Tumors of the endolymphatic sac can result in hearing loss directly through invasion of adjacent sensory structures housed within the otic capsule or indirectly through intralabyrin- thine hemorrhage or endolymphatic hydrops. CN indicates cranial nerve. 42 JAMA, July 4, 2007—Vol 298, No. 1 (Reprinted) ©2007 American Medical Association. All rights reserved. Downloaded from www.jama.com on July 3, 2007 HEARING LOSS ASSOCIATED WITH TUMORS IN VON HIPPEL-LINDAU DISEASE Figure 2. Distribution of Ears With Endolymphatic Sac Tumors 38 Total ears with audiovestibular symptoms 7 Ears with otic capsule 31 Ears without otic capsule invasion invasion 7 Ears with sensorineural 27 Ears with sensorineural 4 Ears without sensorineural hearing loss hearing loss hearing loss 14 Ears with sudden onset of 13 Ears with gradual onset of sensorineural hearing loss sensorineural hearing loss 11 Ears with intralabyrinthine 3 Ears without intralabyrinthine 13 Ears without intralabyrinthine 4 Ears without intralabyrinthine hemorrhage hemorrhage hemorrhage hemorrhage Distribution of 38 ears based on history, imaging, and clinical findings affected by endolymphatic sac tumors in 35 consecutive patients with von Hippel-Lindau disease. logic Assessment” section) at intervals of male [54%]; 16 male [46%]; FIGURE 2). Table. Findings in 38 Ears Affected by 6 to 24 months or when audiovestibular Bilateral ELSTs were detected in
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